Method for the manufacture of 2,6,10,10-tetramethyl-1-oxaspiro 4,5-dec-6-ene

ABSTRACT

Theaspiran is a novel fragrance and flavor substance. Its uses and novel process for making it are disclosed.

FIELD OF THE INVENTION

This invention relates to the fragrance and flavor fields.

SUMMARY OF THE INVENTION

Theaspiran (2,6,10,10-tetramethyl-1-oxaspiro[4,5]-dec-6-ene) of formula IV given in the following Formula Scheme is a known compound disclosed in Tetrahedron Letters 1995 (1969). It has now been found in accordance with the present invention that this compound has special organoleptic properties on the basis of which it is particularly suitable as an odor-and/or flavor-imparting substance.

Theaspiran can be detected in extremely slight concentrations in various essential oils, for example in raspberry oil or in the oil of the yellow passion fruit [see Helv. Chim. Acta 57, 1301 (1974); 55, 1916 (1972); 54, 1881 (1971)]. Nevertheless, the finding that theaspiran is well suited as an odor- and/or flavor-imparting substance must be considered to be surprising since none of these publications contain any reference to the special organoleptic properties of theaspiran.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The invention is accordingly concerned in one of its aspects with odorant and/or flavouring compositions which contain as the essential odour- and/or flavour-imparting ingredient theaspiran in practically pure form or in the form of mixtures (with the exception of natural mixtures containing theaspiran).

By practically pure theaspiran there should be understood, in particular, theaspiran which is free from the accompanying substances which are present in addition to theaspiran in the said natural extracts. As practically pure theaspiran in the scope of the present invention, there should also be understood, for example, synthetically prepared theaspiran.

The theaspiran used in accordance with the invention as an odour- and/or flavour-imparting substance is distinguished by special fresh, fruity odour or flavour properties. Of particular interest is a berry-like, green note and a sweetish, woody nuance appearing with increasing concentration. The theaspiran can accordingly be used, for example, for the perfuming or flavoring of products such as cosmetics (soaps, salves, powders etc), detergents, foods, luxury goods and drinks, the theaspiran preferably not being used alone but in the form of compositions which also contain other odour- or flavour-imparting substances.

In another of its aspects, the invention is concerned with a process for the manufacture of the odorant and/or flavouring compositions aforesaid, which process comprises adding theaspiran in practically pure form or in the form of mixtures (with the exception of natural mixtures containing theaspiran) to known odorant and/or flavouring substance compositions or mixing theaspiran in practically pure form or in the form of mixtures (with the exception of natural mixtures containing theaspiran) with natural or synthetic compounds or mixtures thereof suitable as ingredients of odorant and/or flavouring substance compositions.

Because of its very natural notes, theaspiran is especially suited as an odorant for modifying known compositions; for example, those of the Chypre type. Thus, for example, it is very well suited to combination with flower notes such as, for example, neroli and rose notes.

The concentration of theaspiran in the present compositions can vary within wide limits depending on the purpose of use; for example, between about 1 wt.% (detergents) and about 15 wt.% (alcoholic solutions). In perfume bases or concentrates, the concentrations can of course also be higher.

As a flavour-imparting substance, theaspiran can be used, for example, for the production or improvement, intensification, enhancement or modification of fruit or berry (e.g., raspberry, strawberry, apricot, citrus fruit, pear etc.) flavors in foods (yoghurt, confectionery etc), in luxury goods (tobacco etc) and in drinks (lemonades etc).

The pronounced flavour qualities of practically pure, especially synthetically prepared theaspiran, enables it to be used in low concentrations. A suitable amount lies in the range of 0.00001 ppm - 1 ppm, preferably 0.001 ppm - 0.1 ppm, in the finished product, namely the aromatised feed, luxury goods or drink.

Theaspirane may be added as such or in the form of flavouring agents to the products to be aromatized. In the latter case the flavouring agent can naturally contain other flavouring ingredients, especially those customarily used for the various aforementioned purposes.

The manufacture of odorant or flavourant compositions containing theaspiran can be effected in a manner known per se, see for example Perfume and Flavour Chemicals, S. Arctander, Montclair 1969, Perfume and Flavour Chemicals of Natural Origin, S. Arctander, 1960, Food Flavourings, Composition, Manufacture and Use, 2nd, ed., J. Merory, Westport 1968. Thus, flavouring agents may contain e.g. from 0.01 ppm-5°/oo of theaspiran.

Some effects which can be produced with theaspiran are compiled in the following Table.

                  Table                                                            ______________________________________                                         Aroma      Amount         Effect                                               ______________________________________                                         Tobacco   0.005 ppm in the                                                                              Better tenacity                                       (Top flavour)                                                                            finished product                                                                              aroma; intensified                                                             fruitier impres-                                                               sion.                                                 Vanilla   0.03 ppm in the                                                                               Rounding-off                                                    finished product                                                                              effect; woody                                                                  nuance.                                               Raspberry 0.001 ppm in the                                                                              Rounding-off                                                    finished product                                                                              effect; pleasant,                                                              woody natural                                                                  nuance.                                               ______________________________________                                    

Theaspiran can be mixed with the ingredients used for flavouring substance compositions or added to such flavorants in the usual manner. By the flavorants used in accordance with the present invention there are to be understood flavouring substance compositions which can be diluted or dispersed in edible materials in a manner known per se. They can be converted according to methods known per se into the usual forms of use such as solutions, pastes or powders. The products can be spray-dried, vacuum-dried or lyophilised.

In the production of the aforementioned usual forms of use, the following carrier materials, thickening agents, flavour-improvers, spices, auxiliary ingredients and the like may, for example, be mentioned:

Gum arabic, tragacanth, salts or brewer's yeast, alginates, carrageens or similar absorbants, indoles, maltol, dienals, spice oleoresins, smoke flavors, cloves, diacetyl, sodium citrate, monosodium glutamate, disodium inosine-5'-monophosphate (IMP), disodium guanosine-5-phosphate (GMP), special flavor-imparting substances, water, ethanol, propylene glycol and glycerine.

From the foregoing it will be appreciated that the invention also includes within its scope a method of imparting an odour and/or a flavour to materials by applying thereto or incorporating therein an odorant and/or flavoring composition as hereinbefore defined or theaspiran in practically pure form or in the form of mixtures (with the exception of natural mixtures containing theaspiran).

The present invention is also concerned with a novel improved process for the manufacture of theaspiran, which process comprises treating 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidine)-butan-2-ol of formula III in the following Formula Scheme with an acid.

Especially suitable acids are protonic acids such as inorganic and organic protonic acids (e.g. sulphuric acid, phosphoric acid, p-toluenesulphonic acid etc) or Lewis acids (e.g., BF₃, SnCl₄, ZnCl₂, etc). p-Toluenesulphonic acid is the preferred protonic acid.

The cyclization of 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-ol of formula II to theaspiran of formula IV can be carried out in the presence or absence of a solvent. Suitable solvents are inert solvent such as hexane, benzene, nitromethane, chlorinated hydrocarbons (e.g. chloroform etc) and ethers (e.g. dioxane etc). Benzene and toluene are the preferred solvents. The temperature is not critical; the treatment can be carried out at room temperature or at a higher or lower temperature.

Since it is known that theaspiran can be oxidised to the flavour-imparting substance theaspirone of formula V in the following Formula Scheme (see, for example, U.S. Pat. No. 3,645,755), the process provided by the present invention also provides an advantageous access to theaspirone. The preparation of theaspirone by oxidising theaspiran (prepared according to the foregoing process) in accordance with methods known per se also forms part of this invention.

                                      Formula Scheme                               __________________________________________________________________________      ##STR1##                                                                                            ##STR2##                                                 β-Ionone        4-(2,6,6-Trimethyl-2-                                                          cyclohexen-1-ylidene)-2-                                                       acyloxy-but-2-ene                                                              R = acyl such as lower                                                         alkanoyl e.g. acetyl or                                                        aroyl, e.g. benzoyl.                                       ##STR3##                                                                                            ##STR4##                                                 2,6,10,10-Tetramethyl-1-                                                                            4-(2,6,6-Trimethyl-2-                                     oxaspiro[4,5]-dec-6-ene                                                                             cyclohexen-1-ylidene)-                                                         butan-2-ol                                                 ##STR5##                                                                      2,6,10,10-Tetramethyl-                                                         1-oxaspiro[4,5]-dec-6-                                                         en-8-one                                                                       __________________________________________________________________________

Having regard to the foregoing Formula Scheme, the alcohol of formula III can be obtained from an acyloxy compound of formula II which, in turn, can be obtained from β-ionone of formula I. An acyloxy compound of formula II can be converted into the alcohol of formula III using, for example, a complex hydride such as lithium borohydride, sodium borohydride, potassium borohydride, lithium aluminium hydride etc. The reaction is expediently carried out in an alcohol, for example an alkanol, an alcohol/ether mixture or an ether as the solvent. The temperature at which the reaction is carried out is not critical. It is, however, preferred to carry out the reaction at a temperature of ca -10° C to 80° C.

An acyloxy compound of formula II can be obtained by reacting β-ionone of formula I with an enol acylate. Suitable enol acylates are isopropenyl acetate, isobutenyl acetate etc. The formation of an acyloxy compound of formula II is expediently carried out in the presence of catalytic amounts of acids (e.g. one of the aforementioned acids). p-Toluenesulphonic acid is the preferred acid. The enol acylate is expediently used in excess, whereby it also serves as the solvent. The reaction is preferably carried out at the reflux temperature of the reaction mixture and the ketone (acetone in the case of isopropenyl acetate) formed during the reaction is continuously removed by distillation.

It will be appreciated that formulae II and III include the four possible stereoisomers. Likewise, formulae IV and V include both diastereomeric compounds (i.e. both enantiomeric pairs).

The following Examples illustrate the present invention:

EXAMPLE 1

96 g of β-ionone are dissolved in 500 ml of isopropenyl acetate and treated with 0.6 g of p-toluenesulphonic acid monohydrate. The mixture is stirred at reflux temperature under an inert gas atmosphere for 24 hours. The excess isopropenyl acetate is distilled off from the mixture under a vacuum (temperature ≦50° ) and then the mixture is treated several times with hexane in order to liberate residual amounts of isopropenyl acetate and concentrated again. In this manner, there are obtained 108 g of brown-red 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-2-acetoxy-but-2-ene (formula II; R = acetyl).

UV (ethanol): λ_(max) = 279 nm, log ε = 4, 265

IR (film): 1755, 1650, 1580, 1370, 1220/1205, 1150/1140, 1040, 1020, 945, 925, 885/875/865, 818 cm.sup.⁻¹.

NMR (CDCl₃ + TMS): δ = 6.65 - 5.85 (2H, m); δ = 5.78 (1H, broad t); δ = 2.20 and 2.15 (3H, each S); δ = 2.05 (3H, broad S); δ = 1.85 (3S, narrow m); δ = 1.28 ppm (6H, S). Ms: m/e: 234, fragments at 192, 177, 159, 149, 136, 121, 107, 91, 81, 77, 71, 65, 55, 43 = base peak.

The resulting crude acetoxy compound of formula II (108 g) is dissolved in 400 ml of ethanol (96%) and added dropwise within 10 minutes at 20°-30° C with slight cooling to a suspension of 20 g of sodium borohydride in 600 ml of 96% ethanol. The mixture is then heated until a slight reflux occurs and stirred at this temperature for 15 minutes. The end of the reaction can be detected by a spontaneous colour change from dark-yellow to lemon-yellow. After cooling to room temperature, the cloudy mixture is poured on to saturated ammonium chloride solution/ice and the mixture is extracted with hexane. After the usual washing to neutrality with water and drying over anhydrous sodium sulphate, the solvent is evaporated under a vacuum. There are obtained 96 g of crude 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-ol (formula III).

UV (ethanol: λ_(max) : 239 nm (log ε = 4).

IR (film): 3300, 1380/1370/1360, 1125, 1085, 950, 880, 830 cm.sup.⁻¹.

NMR (CDCl₃ + TMS). ε = 5.7 (1H, broad t); δ = 5.4 (1H, t with J = 7 Hz); δ = 3.9 (1H, m with J = 6Hz); δ = 2.55 (2H, broad t with J = 7 Hz); δ = 1.85 (3H, narrow m); δ = 1.25 (3H, d with J = 6Hz); ε = 1.23 ppm (6H, S).

MS: m/e: 194, fragments at 189, 161, 150, 135 = base, 121, 107, 93, 79, 69, 55, 45, 41.

96 g of the crude alcohol of formula III are heated to reflux in 1.3 liters of absolute benzene in the presence of 1 g of p-toluenesulphonic acid monohydrate for 10 hours. The solution is poured on to a cold saturated bicarbonate solution and extracted with hexane. After washing to neutrality and drying the extract over sodium sulphate, the solvent is evaporated in vacuo. The resulting 96 g of brown oily crude theaspiran of formula IV are separated from the first runnings and residue by short-path distillation. Yield: 77 g. of theaspiran of formula IV; boiling point = 75° C/0.2 mm Hg; n_(D) ²⁰ = 1.492.

IR (film): 1475, 1455, 1380, 1360, 1285, 1195, 1160/1150, 1130, 1110/1085/1080/1060, 1040, 1005, 990, 975, 930, 910/900, 880, 825, 775, 725 cm.sup.⁻¹.

NMR (CDCl₃ + TMS):

Isomer A

δ = 5.25 (1H, narrow m); δ = 4.1 (1H, broad m); δ = 1.75 (3H, narrow m); δ = 1.26 (3H, d with J = 6Hz); δ = 0.95 and 0.88 ppm (each 3H, s).

Isomer B

δ = 5.40 (1H, narrow m); δ = 4.05 (1H, broad m); δ = 1.7 (3H, narrow m); δ = 1.28 (3H, d with J = 6Hz); δ = 1.00 and 0.88 ppm (each 3H, s).

MS: m/e: 194, fragments at 179, 151, 135 = base peak, 123, 109, 96, 82, 77, 67, 55, 41.

EXAMPLE 2

5.7 g (30 mmol) of theaspiran are dissolved in 60 ml of anhydrous tert.butanol and treated within 2 hours at 40° C with 120 ml (ca 30 mmol of CrO₃) of tert.butylchromate solution [150 g of CrO₃, 400 ml of tert.butanol, 140 ml of acetic anhydride]. The mixture is then stirred at 40° C. A further 20 ml of tert.butylchromate solution are added dropwise after 8 days and the same amount is added after 10 days. After a total of 16 days, the mixture is worked-up. The mixture is taken up in 1 liter of methylene chloride, covered with ice and stirred for 1 hour with 1 liter of sulphite/bisulphite solution [40 g of sodium bisulphite, 50 g of sodium sulphite, 1 liter of water]. The mixture is subsequently washed neutral with saturated sodium bicarbonate solution and water, dried over magnesium sulphate and evaporated to dryness. There are obtained 3.0 g of a yellow oil which is purified by column chromatography on a 30-fold amount of silica gel (particle size 0.063-0.200 mm) using hexane/ether mixtures containing 5-10% ether. The yield is 20% of theaspirone of boiling point 88° C/0.12 mm Hg.

UV (ethanol): λ_(max) = 235 nm (ε = 11740).

MS: m/e: 208 = M+, 193, 175, 152, 110, 96, 82, 69, 55, 41. IR (film): 1675, 1630, 1480, 1450, 1390/80/70, 1345, 1310, 1280, 1270, 1160, 1090, 980, 920, 890 cm.sup.⁻¹.

NMR (CDCl₃ + TMS): 1H at δ = 5.72 (narrow quadruplet with J = 1.5 H₂); 1H at δ = 4.2° centred (multiplet); 3H at δ = 2.01 and δ = 1.99 (each singlet for the two diastereomers); 3H at δ = 1.30 (doublet with J = 6Hz)l 6H at δ = 0.99 and 1.02 (singlet for the gem dimethyl groups).

EXAMPLE 3

                  Example 3                                                        ______________________________________                                         Tobacco flavour (Top Flavour)                                                                      Parts by weight                                            ______________________________________                                                             A          B                                               Methylcyclopentenolone                                                                             2.0        2.0                                             Ethyl acetate       2.0        2.0                                             Ethyl anisate       4.0        4.0                                             Butyl formate       4.0        4.0                                             Cinnamaldehyde      7.0        7.0                                             Capric aldehyde (10% in ethanol)                                                                   10.0       10.0                                            Vanillin            10.0       10.0                                            Amyl Salicylate     10.0       10.0                                            C.sub.14 -Aldehyde (10% in ethanol)                                                                10.0       10.0                                            Ethylvanillin       20.0       20.0                                            Heliotropin         20.0       20.0                                            Propyl acetate      25.0       25.0                                            Amyl formate        25.0       25.0                                            Isoamyl acetate     25.0       25.0                                            Coumarin            60.0       60.0                                            Ethyl butyrate      75.0       75.0                                            Benzaldehyde        110.0      110.0                                           Benzyl benzoate     250.0      250.0                                           Theaspiran          --         5.0                                             Ethanol             331.0      326.0                                                               1000.0     1000.0                                          ______________________________________                                    

Composition B has a much fruitier aroma compared with composition A and persists substantially longer than composition A.

A 10% ethanolic solution of this top flavour is sprayed onto fresh cut tobacco, e.g. 2-10 g of the 10% solution onto 50 g of tobacco.

EXAMPLE 4

                  Example 4                                                        ______________________________________                                         Vanilla flavour     Parts by weight                                            ______________________________________                                                             A          B                                               Guaiacol (1% in ethanol)                                                                           1.0        1.0                                             Heliotropin (1% in ethanol)                                                                        1.0        1.0                                             Isoeugenol (1% in ethanol)                                                                         2.0        2.0                                             p-Hydroxybenzaldehyde (1% in                                                   ethanol)            3.0        3.0                                             Vanillin            20.0       20.0                                            Ethylvanillin       120.0      120.0                                           Theaspiran (1% in ethanol)                                                                         --         3.0                                             Ethanol             853.0      850.0                                                               1000.0     1000.0                                          ______________________________________                                    

Composition B differs organoleptically in a very advantageous manner from the composition A which is a conventional vanilla aroma. In particular, the theaspiran imparts a weakly woody and fruity note, by which means the vanilla fragrance is rounded off in a remarkable manner.

100 g of the above vanilla flavour are incorporated (using methods known per se) into 100 kg of caramel (milk/cream) toffees.

EXAMPLE 5

                  Example 5                                                        ______________________________________                                         Raspberry flavour   Parts by weight                                            ______________________________________                                                             A          B                                               Leaf alcohol        1          1                                               Heliotropin         1          1                                               Maltol              2          2                                               Bergamotte oil      3          3                                               Citral              12         12                                              Diethyl succinate   13         13                                              C.sub.14 -Aldehyde  15         15                                              Jasmin absolute     15         15                                              Celery oil          16         16                                              Anethole            21         21                                              Ethyl valerate      21         21                                              Methyl anthranilate 22         22                                              Yara-Yara           26         26                                              C.sub.16 -Aldehyde  30         30                                              Cinnamic alcohol    36         36                                              Vanillin            40         40                                              Indole              38         38                                              Ethyl acetate       58         58                                              β-Ionone       630        630                                             Theaspiran (1% in ethanol)                                                                         --         10                                                                  1000       1000                                            ______________________________________                                    

Composition B has a substantially more rounded-off action, is less obtrusively sweet and is more natural than composition A. The composition B provides a very pleasant, woody undertone.

100 g of the above flavour composition are incorporated into 100 kg of hard boild sweets (hard candy), using methods known per se.

EXAMPLE 6

                  Example 6                                                        ______________________________________                                         Pear flavour        Parts by weight                                            ______________________________________                                                             A          B                                               Eugenol             1.0        1.0                                             Geraniol            1.0        1.0                                             Maltol              1.0        1.0                                             Anethole (10% in ethanol)                                                                          2.0        2.0                                             Vanillin            2.0        2.0                                             Piperonyl acetate   2.5        2.5                                             Geranyl propionate  5.0        5.0                                             Linalyl acetate     10.0       10.0                                            Amyl acetate        100.0      100.0                                           Ethanol             875.5      875.5                                           Theaspiran          --         5                                                                   1000.0     1005.0                                          ______________________________________                                    

Composition B has a substantially rounder and fresher action than the composition A. Further, a pleasant woody undertone can also be detected in composition B.

50 g of the above flavour composition are used to aromatize 100 kg of jelly, using methods known per se.

EXAMPLE 7

                  Example 7                                                        ______________________________________                                         Composition (Fougere) Parts by weight                                          ______________________________________                                         Bergamotte oil        200                                                      Amyl salicylate       150                                                      Coumarin              100                                                      Rhodinol extra        50                                                       Linalool              50                                                       Phenylethyl alcohol   30                                                       Citronellol           30                                                       Tree moss absolute (50% in ethyl                                               phthalate)            20                                                       Patchouli oil         20                                                       Eugenol               10                                                       Lilial                40                                                       Linalyl acetate       100                                                      Alcohol 95°    150                                                      Theaspiran (10% in ethyl phthalate)                                                                  50                                                                             1000                                                     ______________________________________                                    

By the addition of theaspiran, a very original Fougere composition can be produced from an initially conventional Chypre composition; especially remarkable is the aromatic fragrance reminiscent of woodland soil.

EXAMPLE 8

                  Example 8                                                        ______________________________________                                         Composition           Parts by weight                                          ______________________________________                                         Petitgrain oil Paraguay                                                                              400                                                      Geraniol extra        200                                                      Phenylethyl alcohol   160                                                      Methyl anthranilate   160                                                      p-Methylquinoline (10% in ethanol)                                                                   10                                                       Theaspiran (10% in diethyl                                                     phthalate)            70                                                                             1000                                                     ______________________________________                                    

The initially slightly original flowery composition (neroli) has a substantially more rounded-off action and is fuller, softer and sweeter by the addition of theaspiran. The impression of a fresh, natural blossom fragrance is striking. 

What is claimed is:
 1. A process for the manufacture of theaspiran, which process comprises treating 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-ol with an acid.
 2. A process according to claim 1, wherein a protonic acid is used as the acid.
 3. A process according to claim 1, wherein the 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-butan-2-ol is obtained by treating a 4-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-2-acyloxy-but-2-ene with a complex hydride.
 4. A process according to claim 3, wherein sodium borohydride is used as the complex hydride.
 5. A process according to claim 1, wherein theaspiran obtained is converted into theaspirone by oxidation. 